MicroRNA-20b promotes cell growth of breast cancer cells partly via targeting phosphatase and tensin homologue (PTEN)

BACKGROUND: MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that play important roles in multiple biological processes. MiR-20b has been reported to participate in breast cancer tumorigenic progression, however, the functional roles are still unclear and under debating. The aim of this study is to explicit the molecular mechanism of miR-20b underlying breast cancer tumorigenesis. RESULTS: In the present study, we showed that miR-20b was overexpressed in human breast cancer tissues and cell lines compared with paired adjacent normal tissues and normal cell lines, respectively. We identified PTEN, a well-known tumor suppressor, as the functional downstream target of miR-20b. Luciferase assays confirmed that miR-20b could directly bind to the 3′ untranslated region(UTR) of PTEN and suppress translation. Alteration of miR-20b expression changed PTEN protein level but not mRNA expression in ZR-75-30 and MCF-7 breast cancer cells, suggesting miR-20b regulates PTEN gene expression at the posttranscriptional level. Furthermore, upregulation of miR-20b significantly promoted the proliferation, colony formation and DNA synthesis of ZR-75-30 and MCF-7 breast cancer cells. Conversely, knockdown of miR-20b expression inhibited the growth of breast cancer cells in vitro and in vivo. CONCLUSION: Dysregulation of miR-20b plays critical roles in the breast cancer tumorigenesis, at least in part via targeting the tumor suppressor PTEN. This microRNA may serve as a potential diagnostic marker and therapeutic target for breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2045-3701-4-62) contains supplementary material, which is available to authorized users

A Brief Review of OPT101 Sensor Application in Near-Infrared Spectroscopy Instrumentation for Intensive Care Unit Clinics

The optoelectronic sensor OPT101 have merits in advanced optoelectronic response characteristics at wavelength range for medical near-infrared spectroscopy and small-size chip design with build-in trans-impedance amplifier. Our lab is devoted to developing a series of portable near-infrared spectroscopy (NIRS) devices embedded with OPT101 for applications in intensive care unit clinics, based on NIRS principle. Here we review the characteristics and advantages of OPT101 relative to clinical NIRS instrumentation, and the most recent achievements, including early-diagnosis and therapeutic effect evaluation of thrombus, noninvasive monitoring of patients\u27 shock severity, and fatigue evaluation. The future prospect on OPT101 improvements in noninvasive clinical applications is also discussed

Diversifying the Mixture-of-Experts Representation for Language Models with Orthogonal Optimizer

The Mixture of Experts (MoE) has emerged as a highly successful technique in deep learning, based on the principle of divide-and-conquer to maximize model capacity without significant additional computational cost. Even in the era of large-scale language models (LLMs), MoE continues to play a crucial role, as some researchers have indicated that GPT-4 adopts the MoE structure to ensure diverse inference results. However, MoE is susceptible to performance degeneracy, particularly evident in the issues of imbalance and homogeneous representation among experts. While previous studies have extensively addressed the problem of imbalance, the challenge of homogeneous representation remains unresolved. In this study, we shed light on the homogeneous representation problem, wherein experts in the MoE fail to specialize and lack diversity, leading to frustratingly high similarities in their representations (up to 99\% in a well-performed MoE model). This problem restricts the expressive power of the MoE and, we argue, contradicts its original intention. To tackle this issue, we propose a straightforward yet highly effective solution: OMoE, an orthogonal expert optimizer. Additionally, we introduce an alternating training strategy that encourages each expert to update in a direction orthogonal to the subspace spanned by other experts. Our algorithm facilitates MoE training in two key ways: firstly, it explicitly enhances representation diversity, and secondly, it implicitly fosters interaction between experts during orthogonal weights computation. Through extensive experiments, we demonstrate that our proposed optimization algorithm significantly improves the performance of fine-tuning the MoE model on the GLUE benchmark, SuperGLUE benchmark, question-answering task, and name entity recognition tasks.ECAI 202

Loss of OVOL2 in Triple-Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT-Ovol2 knockout mice develop a higher number of primary breast tumors with accelerated growth and increased lung-metastases. Furthermore, treatment with FAO inhibitors effectively reduces stemness characteristics of tumor cells, breast tumor initiation, and metastasis, especially in OVOL2-deficient breast tumors. The findings suggest that targeting JAK/STAT3 pathway and FAO is a promising therapeutic strategy for OVOL2-deficient TNBC

Cytokeratin expression during mouse embryonic and early postnatal mammary gland development

Cytokeratins are intermediate filament proteins found in most epithelial cells including the mammary epithelium. Specific cytokeratin expression has been found to mark different epithelial cell lineages and also to associate with putative mammary stem/progenitor cells. However, a comparative analysis of the expression of cytokaratins during embryonic and postnatal mammary development is currently lacking. Moreover, it is not clear whether the different classes of putative mammary stem/progenitor cells exist during embryonic development. Here, we use double/triple-label immunofluorescence and immunohistochemistry to systematically compare the expression of cytokeratin 5 (K5), cytokeratin 6 (K6), cytokeratin 8 (K8), cytokeratin 14 (K14) and cytokeratin 19 (K19) in embryonic and early postnatal mouse mammary glands. We show that K6+ and K8+/K14+ putative mammary progenitor cells arise during embryogenesis with distinct temporal and spatial distributions. Moreover, we describe a transient disconnection of the expression of K5 and K14, two cytokeratins that are often co-expressed, during the first postnatal weeks of mammary development. Finally, we report that cytokeratin expression in cultured primary mammary epithelial cells mimics that during the early stages of postnatal mammary development. These studies demonstrate an embryonic origin of putative mammary stem/progenitor cells. Moreover, they provide additional insights into the use of specific cytokeratins as markers of mammary epithelial differentiation, or the use of their promoters to direct gene overexpression or ablation in genetic studies of mouse mammary development

Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation

Recent studies have unequivocally identified multipotent stem/progenitor cells in mammary glands, offering a tractable model system to unravel genetic and epigenetic regulation of epithelial stem/progenitor cell development and homeostasis. In this study, we show that Pygo2, a member of an evolutionarily conserved family of plant homeo domain–containing proteins, is expressed in embryonic and postnatal mammary progenitor cells. Pygo2 deficiency, which is achieved by complete or epithelia-specific gene ablation in mice, results in defective mammary morphogenesis and regeneration accompanied by severely compromised expansive self-renewal of epithelial progenitor cells. Pygo2 converges with Wnt/β-catenin signaling on progenitor cell regulation and cell cycle gene expression, and loss of epithelial Pygo2 completely rescues β-catenin–induced mammary outgrowth. We further describe a novel molecular function of Pygo2 that is required for mammary progenitor cell expansion, which is to facilitate K4 trimethylation of histone H3, both globally and at Wnt/β-catenin target loci, via direct binding to K4-methyl histone H3 and recruiting histone H3 K4 methyltransferase complexes

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages